During the next year we will carry out a number of studies in globin gene regulation. We will try to obtain alpha globin genomic DNA and use this DNA to map further the deletion resulting in a single alpha-gene-containing chromosome. We will also map the deletions resulting in loss of both alpha genes from certain chromosome 16s in Black and Asian individuals. We ask whether the difference in severity of Hb H disease, and alpha-thalassemia, in these two racial groups is related to the size and location of the alpha gene deletions. We will also try to develop a specific DNA analysis which differentiates the beta A and beta S genes using a restriction endonuclease specific for the mutation site in the beta A gene. In the field of globin gene transcription, we will try to measure alpha and beta globin transcript ratios in developing spleen cells to compare them with the known alpha/beta ratio of 1.3 in nuclear RNA of these cells. We will also study the 5 feet capping and methylation of globin precursor RNAs. Studies of transcription of globin genes in vitro with purified RNA polymerase II will be continued.